Stage-specific deletion of Olig2 conveys opposing functions on differentiation and maturation of oligodendrocytes

The temporal and spatial patterning involved in the specification, differentiation, and myelination by oligodendroglia is coordinated in part by the activation and repression of various transcriptional programs. Olig2 is a basic helix-loop-helix transcription factor necessary for oligodendroglial de...

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Bibliographic Details
Published in:The Journal of neuroscience 2013-05, Vol.33 (19), p.8454-8462
Main Authors: Mei, Feng, Wang, Hongkai, Liu, Shubao, Niu, Jianqin, Wang, Lingyun, He, Yangtao, Etxeberria, Ainhoa, Chan, Jonah R, Xiao, Lan
Format: Article
Language:English
Subjects:
2',3'-Cyclic-Nucleotide Phosphodiesterases - genetics
2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism
Animals
Animals, Newborn
Arabidopsis Proteins - metabolism
Basic Helix-Loop-Helix Transcription Factors - deficiency
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Basic Helix-Loop-Helix Transcription Factors - ultrastructure
Bromodeoxyuridine - metabolism
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cuprizone - toxicity
Demyelinating Diseases - chemically induced
Demyelinating Diseases - metabolism
Gene Expression Regulation, Developmental - drug effects
Gene Expression Regulation, Developmental - genetics
Green Fluorescent Proteins - genetics
In Situ Nick-End Labeling
Intracellular Signaling Peptides and Proteins - metabolism
Intramolecular Transferases - metabolism
Male
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Monoamine Oxidase Inhibitors - toxicity
Myelin Basic Protein - metabolism
Myelin Proteolipid Protein - genetics
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nerve Tissue Proteins - ultrastructure
Oligodendrocyte Transcription Factor 2
Oligodendroglia - drug effects
Oligodendroglia - physiology
ran GTP-Binding Protein - metabolism
Transfection
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Summary:The temporal and spatial patterning involved in the specification, differentiation, and myelination by oligodendroglia is coordinated in part by the activation and repression of various transcriptional programs. Olig2 is a basic helix-loop-helix transcription factor necessary for oligodendroglial development and expressed continuously throughout the lineage. Despite evidence for the critical role of Olig2 in oligodendroglial specification and differentiation, the function for Olig2 during later stages of oligodendroglial development, namely, the transition into mature oligodendrocytes (OLs) and the formation of the myelin sheath, remains unclear. To address the possibility for a stage-specific role, we deleted Olig2 in oligodendrocyte precursor cells (OPCs) under the control of the CNPase-promoter or in immature OLs under the inducible proteolipid protein promoter. As expected, ablation of Olig2 in OPCs significantly inhibits differentiation, resulting in hypomyelination. However, deletion of the Olig2 gene in immature OLs significantly enhances the maturation process and accelerates the kinetics of myelination/remyelination. Underlying the stage-specific roles for Olig2 is the compensatory expression and function of Olig1, a transcription factor that promotes OL maturation and (re)myelination. Olig1 expression is significantly reduced upon Olig2 deletion in OPCs but is dramatically increased by nearly threefold when deleted in immature OLs. By enforcing expression of Olig1 into OPCs in a null Olig2 background, we demonstrate that overexpression of Olig1 is sufficient to rescue the differentiation phenotype and partially compensates for the Olig2 deletion in vitro. Our results suggest a stage-specific regulatory role for Olig2, mediated by Olig1 that conveys opposing functions on the differentiation and maturation of oligodendrocytes.
ISSN:0270-6474
1529-2401
1529-2401
DOI:10.1523/jneurosci.2453-12.2013